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A BET inhibitor, NHWD-870, can downregulate dendritic cells maturation via the IRF7-mediated signaling pathway to ameliorate imiquimod-induced psoriasis-like murine skin inflammation.
Jin, Liping; Dong, Liang; Pei, Shiyao; Chen, Xiang; Kuang, Yehong; Chen, Wangqing; Zhu, Wu; Yin, Mingzhu.
Afiliación
  • Jin L; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, 410008, China; Furong Laboratory, Changsha, Hunan, 410008, China; Hunan Key Laboratory o
  • Dong L; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, 410008, China; Furong Laboratory, Changsha, Hunan, 410008, China; Hunan Key Laboratory o
  • Pei S; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, 410008, China; Furong Laboratory, Changsha, Hunan, 410008, China; Hunan Key Laboratory o
  • Chen X; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, 410008, China; Furong Laboratory, Changsha, Hunan, 410008, China; Hunan Key Laboratory o
  • Kuang Y; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, 410008, China; Furong Laboratory, Changsha, Hunan, 410008, China; Hunan Key Laboratory o
  • Chen W; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, 410008, China; Furong Laboratory, Changsha, Hunan, 410008, China; Hunan Key Laboratory o
  • Zhu W; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, 410008, China; Furong Laboratory, Changsha, Hunan, 410008, China; Hunan Key Laboratory o
  • Yin M; Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC), Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Chongqing University, Wanzhou, Chongqing, China. Electronic address: yinmingzhu2008@126.com.
Eur J Pharmacol ; 968: 176382, 2024 Apr 05.
Article en En | MEDLINE | ID: mdl-38311277
ABSTRACT
Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of dendritic cells (DCs), which are primarily responsible for initiating an immune response. The bromodomain and extraterminal domain (BET) family plays a pivotal role in the transcriptional regulation of inflammation and its inhibitors can downregulate DCs maturation and activation. Here we investigated the effect of NHWD-870, a potent BET inhibitor, on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS) and IMQ. Application of NHWD-870 significantly ameliorated IMQ-triggered skin inflammation in mice, and markers associated with DC maturation (CD40, CD80 and CD86) were decreased in skin lesions, spleen and lymph nodes. Additionally, NHWD-870 reduced LPS or IMQ induced DCs maturation and activation in vitro, with lower expression of inflammatory cytokines [interleukin (IL)-12, IL-23, tumor necrosis factor-α, IL-6, IL-1ß, chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10]. In addition, we found that interferon regulatory factor 7 (IRF7) significantly increased during DCs maturation, and inhibition of IRF7 could impair BMDCs maturation and activation. What's more, IRF7 was highly expressed in both psoriatic patients and IMQ-induced psoriasis-like mice. Single-cell RNA sequencing of normal and psoriatic skin demonstrated that IRF7 expression was increased in DCs of psoriatic skin. While NHWD-870 could inhibit IRF7 and phosphorylated-IRF7 expression in vivo and in vitro. These results indicate that NHWD-870 suppresses the maturation and activation of DCs by decreasing IRF7 proteins which finally alleviates psoriasis-like skin lesions, and NHWD-870 may be a potent therapeutic drug for psoriasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Psoriasis / Dermatitis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Psoriasis / Dermatitis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos